UNUSUAL PRESENTATION OF AN USUAL CAUSE OF THROMBOCYTOPENIA SOUTHERN RAILWAY HQ HOSPITAL, PERAMBUR DR. KUMARAN DNB PG

UNUSUAL PRESENTATION OF AN USUAL CAUSE OF THROMBOCYTOPENIA SOUTHERN RAILWAY HQ HOSPITAL, PERAMBUR DR. KUMARAN DNB PG

5 months old female infant hailing from Thoothukudi brought by her mother referred from outside for decreased platelet count HOPI An apparently normal child till 3 months of age then developed H/o Fever 10 days H/o Black colored stools on day 7 of illness 2 episodes H/o GTCS on the same day - 1 episode baby hospitalised

On next day - Progressive abdominal distension, respiratory distress, oliguria treated with iv fluids Symptoms improved with in 24 hrs Investigations showed dengue NS1, IgM &IgG positive CBC- thrombocytopenia ( 12000 cells/µl) with lymphocytic leucocytosis LFT, RFT, S.Eletrolytes, UrineR/E, Stool R/E-WNL PT, aptt - WNL

Child had severe persistant thrombocytopenia (7000-15000 cells /µl) for more than 10 days FURTHER INVESTIGATONS.. S.ferritin(721 ng/ml) & S.TGL-464 mg/dl S.Fibrinogen (1.7gm/L)

Bone marrow - reactive nomocellular.(23/01/13) Hospitalised for 17days 1blood & 3FFP transfusions iv antibiotics, zinc, MV drops. IVIG 5 days started on D 10 Child discharged with zinc & MV drops Advice :review after 10 days Review CBC thrombocytopenia Baby referred to our hospital

IN OUR HOSPITAL Baby received in our hospital on 12-02-13 No H/o vomiting / loose stools/jaundice No H/o poor feeding/lethargy/ poor wt gain No H/o other bleeding manifestations No H/o incessant cry/dysuria/ear discharge.

No significant past H/o. Antenatal, Natal & Post natal H/o: uneventful Diet H/o: till now on exclusive breast feeds Normal Developmental milestones. Immunized up to the age.

Family H/o NCM No H/o similar complaints in the family Socio economic H/o: Lower middle class. Contact H/o: No contact with TB

GENERAL EXAMINATION : Child awake, alert, playful. No pallor, icterus, cyanosis, lymphadenopathy. No petechiae, purpura, rash, SCH. Vitals : Stable Anthropometry: WNL SYSTEMIC EXAMINATION : WNL B/L fundus- Normal study

IMP: Persistent thrombocytopenia Post viral(dengue) persistent thrombocytopenia To R/O Autoimmune thrombocytopenia Malignancy HIV congenital thrombocytopenic syndromes Hemophagocytosis

INVESTIGATIONS (12/02/13) Dengue IgG, IgM Positive PS for Mp/Mf- Negative CBC: Hb-10.9 g/dl; Hct-32%; RBCs-4.1M/µl TC-14190 cells/µl DC- P11 M05 L84% Platelets- 26400 cells/µl Serum TGL 320 mg/dl (N: 40 to 165) LFT, RFT, S.Eletrolytes, UrineR/E, Stool R/E-WNL PT, aptt - WNL DCT- negative USG Abdomen- normal study

PERIPHERAL SMEAR(13/02/13) RBC s - normochromic normocytes; normal in count. WBC s - normal in count ; no immature & blast cells. Platelets - Decreased in number. (Thrombocytopenia)

HIV screening negative for both parents

CBC 12/02 13/02 14/02 02/03 08/03 18/03 25/03 02/04 09/04 Hb (g/dl) 10.9 10.4 9.2 9.6 10.1 10.6 10.9 10.8 11.1 Hct (%) 32 29 27 29.2 31.8 33 35 34 35 RBC (M/µl) TC (cells/µl) DC (P/M/L) 4.1 - - 3.3 3.5 3.6-3.75-14190 9000 10400 7900 11400 18010 13400 9700 11500 11/05/ 84 06/07/ 87 07/03/ 90 10/05/ 85 26/01/ 73 07/03/ 90 19/04/ 77 13/02 /85 MCV (fl) 78 - - 87.7 92 92-89.6 - MCH (pg) 27 - - 28.8 32 32.1-28.8-20/05 /75 MCHC (g/dl) PLC (cells/µl) 34 - - 32.9 29.2 29.5-32.1-26400 13000 17000 11400 39200 32400 28000 15000 6000

Rx: Tab. Prednisolone 5mg 1 BD Tab. Folic acid 1 mg 1OD Iron drops 1 ml BD

On day 10 of admission, sub conjunctival hemorrage in left eye.. Platelet count 6000 cells/µl So one platelet transfusion done

21/02/13 to 27/02/13 Re-evaluation in cancer institute Adayar. Baby clinically stable Investigations : Hb, TC, DC - WNL Platelets - 50,000cells/µl IgM Dengue- positive TORCH- Negative Bone marrow- hypercellular; No atypical& blast cells Impression: Persistent post viral thrombocytopenia with no evidence of malignancy.

(09/03/13) S/B consultant Haematologist (Dr. Pushpa) Peripheral smear RBCs- occasional microspherocytes, all RBCs flattened WBCs normal in count ; few WBCs seen engulfing RBCs (erythrophagocytosis) Platelets -Decreased in number (Thrombocytopenia) Serum Ferritin 129 ng/ml (N: 13 to 150) Serum TGL 320 mg/dl (N: 40 to 165)

DISCUSSION PERSISTENT THROMBOCYTOPENIA AFTER DHF

Possible mechanisms a) Bone marrow suppression by virus b) Immune mediated clearance of platelets c) Spontaneous aggregation of platelets to vascular endothelial cell pre-infected by virus inducing aggregation, lysis and platelet destruction d) Anti-platelet antibodies (Ref: INDIAN PAEDIATRICS,nov 2006)

Discussion 2 hemophagocytic syndrome (IAHS): Acute onset pancytopenia with high spiking fever, lymphadenopathy & hepatosplenomegaly Others: Purpura, mucosal bleeding Elevated FDP, prolonged PT, aptt Hypofibrinogenemia Fall in ESR

Diagnostic guidelines 1 or 2 of following criteria: 1) molecular(prf,sap mutations) 2) 5 out of 8 of the following: a) Fever b) Splenomegaly c) Cytopenia (= 2 cell lineages;hb 9 g/dl, platelet 100000/µl, neutrphils 1000/µl) d) Hypertrigycidemia (=265 mg/dl)& or Hypofibinogenemia (=150 mg/d)

e) Hemophagocytosis in BM, spleen or LN without malignancy f) Low or absent NK cell cytotoxicity g) Hyperferritinemia (=500 ng/ml) h) Elevated soluble CD25(IL-2alpha chain= 2400 U/ml)

Our case Hypertrigycidemia (=265 mg/dl Hyperferritinemia (=500 ng/ml)

ARTICLES INDIAN PEDIATRICS Volume 43 November 17, 2006 N.Dinesh, V.D.Patil Studied two children with persistent thrombocytopenia after DHF for more than 1 month Persistent thrombocytopenia in both cases responded to IV Methyl predinosolone.

Pediatric Hematology and Oncology, Management of Severe Refractory Thrombocytopenia in Dengue Hemorrhagic Fever with Intravenous Anti-D Immune Globulin Gaurav Kharya, Satya Prakash Yadav, Satyendra Katewa, Anupam Sachdeva. The authors present their experience of usage of intravenous anti-d in 5 children with DHF and severe refractory thrombocytopenia (<10,000/mm3). It was administered in a dose of 50 to 75 µg/kg. 28:727 732, 2011 Mean platelet count was 6800/mm3 before and 33,600, 44,600, and 79,000/mm3 after intravenous anti-d administration at 24, 48, and 72 hours, respectively. Intravenous anti-d can possibly be a treatment option for refractory thrombocytopenia in DHF.

Present status of child Child is active, well thriving, gaining milestones appropriate for age No active bleeds, no organomegaly, no lymphadenopathy On prednisolone 5mg bd and close observation Mother counselled for prevention of falls and injuries

Take home message Thrombocytopenia in dengue usually lasts for 5-7 days But in rare instances it may last for more than 3 months as in our case We are presenting this case because of its rarity